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A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β
Jeffrey J. Iliff, Minghuan Wang, Yonghong Liao, Benjamin A. Plogg, Weiguo Peng, Georg Andreas Gundersen, Helene Benveniste, George Edward Vates, Rashid Deane, Steven A. Goldman, Erlend Arnulf Nagelhus, Maiken Nedergaard. Science Translational Medicine, 2012-08-15
Topic: Brain proteins, microglia and lab models
Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Iliff, J. J., Wang, M., Liao, Y., Plogg, B. A., Peng, W., Gundersen, G. A., et al. (2012). A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.3003748
Vancouver
Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, et al. A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β. Science Translational Medicine. 2012. doi:10.1126/scitranslmed.3003748. PMID: 22896675.
BibTeX
@article{iliff2012-22896675,
author = {Iliff, Jeffrey J. and Wang, Minghuan and Liao, Yonghong and Plogg, Benjamin A. and Peng, Weiguo and Gundersen, Georg Andreas and Benveniste, Helene and Vates, George Edward and Deane, Rashid and Goldman, Steven A. and Nagelhus, Erlend Arnulf and Nedergaard, Maiken},
title = {{A Paravascular Pathway Facilitates CSF Flow Through the Brain Parenchyma and the Clearance of Interstitial Solutes, Including Amyloid β}},
journal = {Science Translational Medicine},
year = {2012},
doi = {10.1126/scitranslmed.3003748},
pmid = {22896675},
url = {https://doi.org/10.1126/scitranslmed.3003748}
}
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 12 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Why it matters
In animal experiments, cerebrospinal fluid flowed into brain tissue along spaces around arteries and drained along spaces around veins, carrying away solutes including amyloid β. Animals lacking the water channel aquaporin-4 showed about a 70% reduction in solute clearance, and the authors suggest impairment of this pathway may contribute to the buildup of proteins in neurodegenerative conditions.
How this study scored 57/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on strength of evidence, so that was left out: it earned 54 of the 95 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Science Translational Medicine) |
| Journal's citation record | 3 / 4 | Science Translational Medicine: journal h-index 365 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | — / 5 | No evidence rating recorded — left out of this score |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 7 / 7 | Cited 5,777 times (OpenAlex, 2026-10-10) |
| Citations per year | 5 / 5 | 361.1 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 6 / 6 | Cited 46.3× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 4 / 4 | Cited 2,252 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Maiken Nedergaard: h-index 156 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Rochester: institution h-index 1,195 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 3 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22896675) |
| Free to read | 2 / 2 | Free to read |
| Points | 54 / 95 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 54 of the 95 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1126/scitranslmed.3003748
- PubMed: 22896675
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
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